objective: To explore the role and potential mechanism of isochorismatase domain-containing 1 (ISOC1) in gastric cancer. methods: The expression levels of ISOC1 in gastric cancer (GC) tissues, as well as corresponding cell lines, was evaluated by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). A cell line stably expressing ISOC1 was constructed by vector construction and cell transfection, and the proliferation ability of the stably transfected cells was examined. Subsequently, the ISOC1 target database was screened, which suggested that CDK19 may be the potential target. The correlation between ISOC1 and CDK19 mRNA and protein expressions in clinical tissue specimens and cell lines was evaluated by qRT-PCR and Western blot, and the Luciferase reporter gene experiment was applied to verify the regulatory effect of ISOC1 on CDK19. results: ISOC1 was shown to be markedly increased in GC tissues compared to adjacent cancer tissues by qRT-PCR. In addition, compared with patients with low ISOC1 expression, the pathological stage and tumor size of gastric cancer patients with high ISOC1 expression were remarkably larger. Then, the ISOC1 knockdown cell line was established, and it was found through cell proliferation function experiments that the proliferation rate of gastric cancer cells was remarkably slower than the control group after knocking down ISOC1. Subsequently, bioinformatics and Luciferase reporter gene experiments suggested that ISOC1 had a direct regulatory effect on CDK19. In addition, recovery experiments also demonstrated that CDK19 overexpression could reverse the effect of ISOC1 silencing on cell proliferation. conclusions: ISOC1 was markedly upregulated in GC tissues. It could positively regulate its downstream target CDK19, which in turn promoted the proliferation of GC cells. Therefore, our study may provide new ideas for understanding the progression of GC.